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Metropolitan Government of Nashville-Davidson (balance), TN, United States

Ayati B.P.,University of Iowa | Edwards C.M.,Vanderbilt University | Webb G.F.,Vanderbilt University | Wikswo J.P.,Vanderbilt University | Wikswo J.P.,Vanderbilt Institute for Integrative Biosystems Research and Education
Biology Direct | Year: 2010

Background: Multiple myeloma is a hematologic malignancy associated with the development of a destructive osteolytic bone disease.Results: Mathematical models are developed for normal bone remodeling and for the dysregulated bone remodeling that occurs in myeloma bone disease. The models examine the critical signaling between osteoclasts (bone resorption) and osteoblasts (bone formation). The interactions of osteoclasts and osteoblasts are modeled as a system of differential equations for these cell populations, which exhibit stable oscillations in the normal case and unstable oscillations in the myeloma case. In the case of untreated myeloma, osteoclasts increase and osteoblasts decrease, with net bone loss as the tumor grows. The therapeutic effects of targeting both myeloma cells and cells of the bone marrow microenvironment on these dynamics are examined.Conclusions: The current model accurately reflects myeloma bone disease and illustrates how treatment approaches may be investigated using such computational approaches.Reviewers: This article was reviewed by Ariosto Silva and Mark P. Little. © 2010 Ayati et al; licensee BioMed Central Ltd.

Harkness K.M.,Vanderbilt University | Harkness K.M.,Vanderbilt Institute of Chemical Biology | Harkness K.M.,Vanderbilt Institute for Integrative Biosystems Research and Education | Harkness K.M.,Vanderbilt Institute of Nanoscale Science and Engineering | And 7 more authors.
Analyst | Year: 2010

Thiolate-protected gold nanoparticles (AuNPs) are a highly versatile nanomaterial, with wide-ranging physical properties dependent upon the protecting thiolate ligands and gold core size. These nanoparticles serve as a scaffold for a diverse and rapidly increasing number of applications, extending from molecular electronics to vaccine development. Key to the development of such applications is the ability to quickly and precisely characterize synthesized AuNPs. While a unique set of challenges have inhibited the potential of mass spectrometry in this area, recent improvements have made mass spectrometry a dominant technique in the characterization of small AuNPs, specifically those with discrete sizes and structures referred to as monolayer-protected gold clusters (MPCs). Additionally, the unique fragmentation data from mass spectrometry enables the characterization of the protecting monolayer on larger AuNPs. The development of mass spectrometry techniques for AuNP characterization has begun to reveal interesting new areas of research. This report is a discussion of the historical challenges in this field, the emerging techniques which aim to meet those challenges, and the future role of mass spectrometry in the growing field of thiolate-protected AuNPs. © 2010 The Royal Society of Chemistry.

Ashby W.J.,Vanderbilt University | Ashby W.J.,Vanderbilt Institute for Integrative Biosystems Research and Education | Wikswo J.P.,Vanderbilt Institute for Integrative Biosystems Research and Education | Wikswo J.P.,Vanderbilt University | And 2 more authors.
Biomaterials | Year: 2012

Cell migration is controlled by the integration of numerous distinct components. Consequently, the analysis of cell migration is advancing towards comprehensive, multifaceted in vitro models. To accurately evaluate the contribution of an underlying substrate to cell motility in complex cellular environments we developed a migration assay using magnetically attachable stencils (MAts). When attached to a culture surface, MAts create a defined void in the cell monolayer without disrupting the cells or damaging the underlying substrate. Quantitative analysis of migration into this void reveals the substrate's contribution to migration. The magnetically-guided placement of a microfabricated stencil allows for full experimental control of the substrate on which migration is analyzed. MAts enable the evaluation of intact, defined matrix, and make it possible to analyze migration on unique surfaces such as micropatterned proteins, nano-textured surfaces, and pliable hydrogels. These studies also revealed that mechanical disruption, including the damage that occurs during scratch assays, diminishes migration and confounds the analysis of individual cell behavior. Analysis of migration on increasingly complex biomaterials reveals that the contribution of the underlying matrix depends not only on its molecular composition but also its organization and the context in which it is presented. © 2012 Elsevier Ltd.

Goodwin C.R.,Vanderbilt University | Goodwin C.R.,Vanderbilt Institute for Chemical Biology | Goodwin C.R.,Vanderbilt Institute for Integrative Biosystems Research and Education | Fenn L.S.,Vanderbilt University | And 7 more authors.
Journal of Natural Products | Year: 2012

A significant challenge in natural product discovery is the initial discrimination of discrete secondary metabolites alongside functionally similar primary metabolic cellular components within complex biological samples. A property that has yet to be fully exploited for natural product identification and characterization is the gas-phase collision cross section, or, more generally, the mobility-mass correlation. Peptide natural products possess many of the properties that distinguish natural products, as they are frequently characterized by a high degree of intramolecular bonding and possess extended and compact conformations among other structural modifications. This report describes a rapid structural mass spectrometry technique based on ion mobility-mass spectrometry for the comparison of peptide natural products to their primary metabolic congeners using mobility-mass correlation. This property is empirically determined using ion mobility-mass spectrometry, applied to the analysis of linear versus modified peptides, and used to discriminate peptide natural products in a crude microbial extract. Complementary computational approaches are utilized to understand the structural basis for the separation of primary metabolism derived linear peptides from secondary metabolite cyclic and modified cyclic species. These findings provide a platform for enhancing the identification of secondary metabolic peptides with distinct mobility-mass ratios within complex biological samples. © 2012 The American Chemical Society and American Society of Pharmacognosy.

Irvin M.W.,Vanderbilt University | Zijlstra A.,Vanderbilt Institute for Integrative Biosystems Research and Education | Zijlstra A.,Vanderbilt University | Wikswo J.P.,Vanderbilt University | And 3 more authors.
Experimental Biology and Medicine | Year: 2014

The importance of studying angiogenesis, the formation of new blood vessels from pre-existing vessels, is underscored by its involvement in both normal physiology, such as embryonic growth and wound healing, and pathologies, such as diabetes and cancer. Treatments targeting the molecular drive of angiogenesis have been developed, but many of the molecular mechanisms that mediate vascularization, as well as how these mechanisms can be targeted in therapy, remain poorly understood. The limited capacity to quantify angiogenesis properly curtails our molecular understanding and development of new drugs and therapies. Although there are a number of assays for angiogenesis, many of them strip away its important components and/or limit control of the variables that direct this highly cooperative and complex process. Here we review assays commonly used in endothelial cell biology and describe the progress toward development of a physiologically realistic platform that will enable a better understanding of the molecular and physical mechanisms that govern angiogenesis. © 2014 by the Society for Experimental Biology and Medicine.

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